Defining the correlates of protective immunity mediated by Ly6C+CD44+CD62L−CD4+ T effector (TEFF) cells against <i>Leishmania major</i> infection: implications for vaccination against intra-phagosomal pathogens
Bibliographic record
Abstract
Abstract The protozoan Leishmania parasite is a human obligate intra-cellular pathogen and the causative agent of leishmaniasis, a chronic neglected tropical disease of existing and growing global importance. Despite considerable effort a human vaccine does not exist. In the C57Bl/6 mouse model of naturally acquired protective immunity, chronic primary infection maintains short-lived Ly6C+ TEFF cells that mediate protective immunity against secondary challenge. These cells, not memory cells or cells derived from memory cells following challenge, emulate the rapid IFN-g response associated with protective immunity against natural infected sand fly challenge. Defining the mechanisms by which these cells mediate their protective effect will be essential for informing future vaccine design. To elucidate the importance of the rapidity of the Ly6C-mediated response as a protective correlate, the influence of these cells on innate immune cells, and ultimately their capacity to facilitate the priming and activation of Leishmania-specific naïve cells, we devised an adoptive transfer system in which Ly6C+ TEFF cells from chronic mice are transferred into recipient mice at the time of infection or 4 days following infection, just prior to the initiation of parasite replication. Disease progression was followed for 3 weeks and the activation of phagocytes, antigen-presenting cell function, and IFN-g production by both adoptively transferred and recipient populations was analyzed. Our observations are likely to enhance our understanding of the correlates of protective immunity beyond the simple generation of IFN-g producing memory cells, a strategy that has so far failed to generate an effective human vaccine.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".